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B Emmerich

Publications and source records attributed to B Emmerich.

At least 91 records · Page 5Linked to original sources
PubMed1991

Quantitation of mRNA for the beta-adrenoceptor gene in human mononuclear leucocytes by in situ hybridization with fluorochrome labeled cloned DNA.

Determination of the transcriptional activity of the beta-adrenoceptor (beta-AR) gene in human mononuclear leucocytes (MNL) may provide important information concerning variations in receptor expression in clinical studies. We used a new method with highly fluorochrome-labeled gene probes for in situ hybridization which allows a rapid detection of mRNA at the cellular level. MNL from venous blood of healthy volunteers were permeabilized, fixed and attached to adhesive glass slides. After incubation with fluorochrome-labeled cloned hamster beta AR-DNA probes the amount of DNA-mRNA hybrids formed in the cytoplasm of individual cells was analyzed by microfluorimetry of specifically bound fluorochrome. In nine of ten normal subjects studied so far a fraction of beta AR-mRNA positive MNL could be detected. The proportion of positive cells as well as their signal intensity revealed a high interindividual variance.

Adolescent↗
PubMed1991

Detection of cathepsin B in tumor cytosol and urine of breast cancer patients.

In order to evaluate the role of cathepsin B (CB) as a proteinase involved in mammary tumor progression and its potential role as a tumor marker, we have measured the CB activity in cytosols of breast cancer tumor tissue using Z-Arg-Arg-AMC as the substrate and found a 23fold increase when compared to distantly located breast tissue from the same patient. In addition, urine of breast cancer patients under adjuvant chemotherapy was screened for CB immunoreactivity with a sandwich type enzyme immunoassay which revealed significant interindividual differences in concentrations with some urines containing immunoreactivity comparable to healthy controls. The urines were also investigated for CB activity but no differences between patients and controls were observed. However, urine contains thiol activatable proteinases causing substrate hydrolysis, which is to a varying extent inhibited by E-64 or Z-Phe-Phe-CHN2.

Adult↗
PubMed1990

[Interferon alfa-2B in chronic lymphatic leukemia of the B-cell type].

In a clinical phase II study nine patients (five men and four women; mean age 48 [42-58] years) in an early stage of chronic lymphatic leukaemia (CLL) of the B-cell type were treated with recombinant alpha-2b interferon (IFN alpha-2b), initially at a dosage of 5 mega units subcutaneously three times weekly, but in some cases reduced to 2.5 or raised to 10 mega units. Duration of treatment has been 15-36 months. Through-flow cytometry in seven patients demonstrated a definite fall in circulating B1-positive lymphocytes. Lasting partial remission (duration of 106-134 weeks) was achieved in four patients, in a further four the condition remained stable. A recurrence was noted in the patient with the initially highest lymphocyte count (52,000/microliters) after 28 weeks, control being achieved only after 64 weeks of chemotherapy. Side effects were flu'-like symptoms and (in two instances) depression. In three patients there was a clear rise in serum immunoglobulin concentrations as sign of IFN alpha-2b-induced increased immune response, while in four HLA-DR expression on monocytes was doubled. It is concluded that early treatment of CLL with IFN alpha-2b may delay the onset of necessary chemotherapy, any antibody-deficiency may be improved and survival time may ultimately be lengthened.

Adult↗
PubMed1990

Deficient production of tumor necrosis factor by peripheral-blood monocytes in chronic lymphocytic leukemia.

The production of tumor necrosis factor (TNF) by lipopolysaccharide (LPS)-triggered peripheral-blood mononuclear cells (PBM) was investigated in 23 patients with untreated B-cell chronic lymphocytic leukemia (B-CLL) and 14 control donors. Cells were stimulated at concentrations that reflect cell density in peripheral blood. Under these conditions, PBM from 11/23 of the CLL patients produced at least 10-fold less TNF as compared with controls. Monocyte numbers were decreased in percentage, while absolute numbers (normal range 233 +/- 120 X 10(3)/mm3) were decreased only in 2, normal in 17 and increased in 4 patients indicating that the deficiency is not a result of monocytopenia in most patients. Cell separation experiments indicate that after removal of leukemic B cells, percentages of monocytes return to control range and TNF production is improved (7/7). In mixing experiments, we found a suppression of TNF production in control mononuclear cells by CLL cell samples (75 X 10(6) cells/ml) in 5/19 cases, while control cells from thymus exhibited no or little suppression in these conditions. In 2-chamber experiments, leukemic samples suppress TNF production by normal monocytes across a 0.45 micron membrane indicating that a soluble factor is responsible for suppression. The factor exhibits higher stability in serum-free conditions and its molecular weight is below 20 kDa. Prostaglandins are not involved, since indomethacin did not abrogate suppression.

Aged↗
PubMed1990

Changes in clonal growth, immunophenotype, and morphology during a follow-up study of an acute lymphoblastic leukemia.

Cells of a 21-year-old patient with acute lymphatic leukemia were analyzed for morphology and immunophenotype and for genotype consecutively during the course of disease. Initial therapy with the BMFT-ALL protocol (Bundesministerium für Forschung und Technologie) reduced leukemic cells only marginally. The following high-dose Ara-C, mitoxantrone (HAM) chemotherapy led to a cell reduction of 75% and to a drastic change in cell morphology from initially 90% blasts to mainly small lymphoid cells. Immunophenotype, which showed 90% CD7-positive cells in the beginning with a prevalence of helper (60%) over suppressor cells (15%) remained fairly constant until the onset of HAM chemotherapy, which led to a sharp fall and a subsequent slow increase in all T-cell markers. In contrast to pretherapeutic findings, CD7 was now only expressed on the small cells and not on blast cells. Southern blot analysis of the T-cell receptor configuration revealed an initially monoclonal population with rearranged T beta gene. A new band appearing during the clinically ineffective therapy was indicative for development of a second small population which did, however, not emerge in immunophenotype analysis. This second population was eliminated by the HAM chemotherapy, leaving back the initial clone responsible for the final fatal outcome. No activity of the multidrug resistance gene could be detected by Northern blotting.

Adult↗
PubMed1990

Antigen receptor rearrangement and expression in acute leukemias.

Twenty-two leukemias, 11 of which were undifferentiated with respect to surface antigen markers, were investigated for their antigen receptor gene rearrangement, transcription products of these antigen receptor genes, and surface antigen pattern of the cells. Among the three less-differentiated groups rearrangement was observed in 2/10 cases for the TCR beta-chain and in 4/11 cases for the heavy-chain gene. TCR beta-mRNA, however, was expressed in seven out of eight cases and the mu heavy-chain mRNA in eight out of ten cases investigated. Also mRNA of TCR alpha, the rearrangement of which could not be detected with our probes, was expressed as frequently as TCR beta. Although rearrangement of the appropriate gene was found regularly in the more mature leukemias, transcription of these genes was lower or even lacking. These findings indicate that expression of antigen receptor mRNA in undifferentiated leukemias can be activated by events other than maturational rearrangement.

Acute Disease↗
PubMed1990

Effects of a bacterial extract on local immunity of the lung in patients with chronic bronchitis.

Our findings demonstrate that Broncho-Vaxom (BV) displays possibly via the gut-associated immune system different effects on the lymphatic system of the lung: a positive influence on the helper/suppressor T-lymphocyte balance, an increase of gamma interferon, a stimulation of the reduced alveolar macrophage activity, and a regulation of BAL IgA to a distinct level whereby the serum IgE is reduced. By these effects BV is able to modulate impaired local and systemic immune function. The observed relationship between the inflammation score and the BAL fluid composition supports the view that the improvement of the mucosa lesion found in nearly all of our patients with chronic bronchitis occurs as the result of the pleiotropic immunomodulating effects of Broncho-Vaxom.

Adjuvants, Immunologic↗
PubMed1990

Local immunity in patients with chronic bronchitis and the effects of a bacterial extract, Broncho-Vaxom, on T lymphocytes, macrophages, gamma-interferon and secretory immunoglobulin A in bronchoalveolar lavage fluid and other variables.

In 28 adult patients with nonobstructive chronic bronchitis we investigated components of the immune system of the lower airways and the effects of treatment with Broncho-Vaxom (BV). An analysis of the washing from bronchoalveolar lavage (BAL) showed, in comparison with healthy controls, an elevation of total cell count (p = 0.003) as well as the IgA/albumin values (p = 0.02) and a reduction of the macrophage activity (p less than 0.001) in patients with chronic bronchitis. After BV a reduction in the total cell count (p = 0.05), an increase in the helper/suppressor T lymphocyte ratio (due mainly to the reduction in the suppressor cells; p = 0.04), a modulation of the IgA/albumin ratio, a stimulation of the impaired alveolar macrophage activity (p = 0.03) and increased concentrations of gamma-interferon (p = 0.03) were found in the BAL fluid of patients with chronic bronchitis. The salivary IgA/albumin ratio remained unchanged, the serum IgE concentration fell (p = 0.02) and the urinary IgA concentration rose (p = 0.002). Bronchial mucosa lesions, evaluated endoscopically in terms of structural damage, hyperemia and mucus production, were improved (p less than 0.01). These findings indicate that orally administered BV modulates disordered local and systemic immune functions in patients with chronic bronchitis.

Adjuvants, Immunologic↗
PubMed1990

Protein profiles in rabbit pancreatic juice analyzed by HPLC after stimulation of secretion by secretin and cerulein.

This study analyzed the secretory pattern of pancreatic proteins released from the rabbit pancreas after acute stimulation of secretion by the cholecystokinin analog cerulein. To facilitate this, a new analytical approach utilizing high performance liquid chromatography (HPLC) was considered. Secretin (0.1 CU/kg x h) was intravenously infused in anaesthetized rabbits in combination with cerulein (0.05, 0.2 or 0.05 followed by 0.2 ug/kg x h) over 3 hours. Pancreatic juice was collected from the main pancreatic duct. The release of protein, amylase, trypsin and chymotrypsin was measured by conventional photometric methods, and the protein profiles were analyzed by reversed phase HPLC. Separation of pancreatic juice proteins by HPLC (Nucleosil 300-7 RP column; injection of 50 ul aliquots of samples normalized to 10 mg/ml protein concentration) resulted in a resolution of up to 16 peaks. Peaks representing amylase, prolipase, prophospholipase A2, procarboxypeptidases, chymotrypsinogen, trypsinogen, and glycoproteins were identified with some certainty by SDS-gel electrophoresis. Secretin infusion produced a small and short lasting rise in total protein secretion but lead to a persistent increase of fluid flow. The release of enzymes followed a mainly parallel pattern according to the photometric measurements. The resolution of the whole profile of pancreatic juice proteins by HPLC demonstrated only minor variations without a consistent or increasing tendency towards a preferential release of individual enzymes. Since even microheterogenities in the samples became apparent after HPLC, this approach would be sensitive enough to mirror effects like nonparallel release of enzymes.

Animals↗
PubMed1989

Quantitative tracing of mRNAs for T- and B-lymphocyte receptor genes in individual cells by in situ hybridization with fluorochrome-labeled gene probes. I. Expression in malignancies carrying B-lineage associated antigens.

Acute and chronic lymphatic leukemias were investigated on the single-cell level for the activity of genes coding for the IgM heavy chain and the alpha and beta chains of the T-cell antigen receptor (TCR). We used a new method for preparing highly fluorochrome-labeled gene probes for in situ hybridization, which allowed rapid and quantitative detection of mRNA at the individual cell level. Leukemic cell populations classified as belonging to the B lineage according to their surface antigenic patterns revealed increasing expression of mRNA for the IgM heavy chain (mu mRNA) in a maturation-dependent fashion, which was not correlated to rearrangement of the immunoglobulin mu chain gene--only 66% of the leukemias with rearranged mu gene also transcribed it. TCR mRNA was detected in B-antigen positive leukemic cells. High levels of both TCR and mu mRNA expression in all cells of some of these leukemias allowed the conclusion that these cells simultaneously transcribed the genes for T and B cell antigen receptors. TCR mRNA was also found in what are considered relatively mature B leukemias, lineage cross-over on the mRNA level being observed at a frequency of 23% (five of 22 cases), comparable with that of "inappropriate" receptor gene rearrangement. The quantitation of mRNA with fluorochrome-labeled gene probes in situ may allow determining the degree of gene activation in individual antigenically defined cells and may thus contribute a new tool for characterization of normal and malignant cells.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

[The significance of chronopharmacology for oncology].

Many physiological variables in hemato-oncology, e.g. the function of liver and kidney and hematopoiesis, show circadian changes. Consequently, the metabolism, elimination and myelotoxicity of cytostatic drugs are subjected to circadian variations in animal and man. Moreover, preliminary clinical data suggest that an optimal circadian timing may even increase the efficacy of anticancer chemotherapy. The recent development of programmable infusion pumps provided a reliable tool for the application of cytostatic drugs at any time of day. As a consequence, controlled clinical trials on the temporal optimization of anticancer chemotherapy seem now to be necessary and feasible.

Animals↗
PubMed1989

T cell receptor alpha expression in B-type chronic lymphocytic leukemia.

Normal B lymphocytes are characterized by rearrangement and expression of immunoglobulin genes, but not of T cell receptor genes. These properties might assist in lineage assignment, but there are examples of fresh leukemic cells and of cell lines where exceptions to this rule have been noted. We have studied cell samples of patients with B-CLL for expression of TCR alpha and beta chain genes. Using in situ hybridization with fluorescein-labeled probes, TCR alpha mRNA was found to be expressed in 14 of 18 samples and TCR beta mRNA in 7 of 16 samples. Specificity of hybridization was demonstrated by near complete blockade of TCR alpha hybridization with unlabeled TCR alpha, but not with unlabeled TCR beta probe. Furthermore, in Northern blot analysis a truncated 1,4 kb message for TCR alpha was readily detectable. No significant cell surface staining with the anti-TCR alpha/beta monoclonal antibody WT31 was observed. A contribution of T cells within the leukemic sample could be excluded since only samples with leukemic cell counts of greater than 50,000 cells/mm3 and only samples with 5% or less CD2+ T lymphocytes were studied. Our data show that a large proportion of B-CLL samples may express a truncated version of the TCR alpha message, indicating that this gene can be activated in leukemic B cells frozen at a late stage of differentiation.

B-Lymphocytes↗
PubMed1988

Activity of serum thymidine kinase in non-Hodgkin lymphoma: relationship to other prognostic factors.

The value of serum deoxythymidine kinase (TK) for the staging and evaluation of disease activity of non-Hodgkin lymphoma (NHL) as compared with serum beta 2-microglobulin, serum lactate dehydrogenase, blood sedimentation rate, blood hemoglobin, white blood cell count, lymphocyte count and platelet count was investigated in 101 patients. In addition, the performance status was determined by the Karnofsky index. Patients with chronic lymphocytic leukemia (CLL; n = 43) and immunocytoma (IC; n = 19) were staged according to the Binet classification, and the other low (n = 28) and high grade NHL (n = 8) according to the Ann Arbor classification. The analysis of all CLL and IC patients revealed that TK values correlated better with Binet stages (p = 0.01; n = 58) than blood sedimentation rate (p = 0.05, n = 12), lactate dehydrogenase (p = 0.08; n = 50), beta 2-microglobulin (p = 0.29; n = 28), lymphocyte count (p = 0.70; n = 57), white blood cell count (p = 0.69, n = 59) and the Karnofsky index (p = 0.16, n = 50). Mean TK levels of these patients were for Binet stage A 6.2 +/- 0.8 U/l (mean +/- S.E.M., range 2.3-18.0), stage B 13.3 +/- 6.5 U/l (3.8-38.8) and stage C 19.6 +/- 4.4 U/l (1.9-79.0), and for 22 healthy controls 3.8 +/- 0.2 U/l (2.2-6.0). Patients with multiple courses of chemotherapy (n = 32) previous to the study had significantly (p = 0.01) higher TK levels (16.4 +/- 3.7 U/l; 2.3-79.0) than those with only up to one course (n = 66; TK: 8.6 +/- 1.4 U/l; 1.5-66.3). The follow-up of 16 patients with low grade NHL showed that serum TK levels paralleled well the clinical response. The results indicate that TK might be a worthful parameter to estimate progression and response to therapy of NHL.

Adult↗
PubMed1988

Quantitation of mu mRNA by in situ hybridization reveals a correlation between B-maturation associated antigens and IgM gene activation in acute lymphatic leukemias.

Acute lymphatic leukemias, expressing the common acute leukemia antigen were investigated for expression of early T- and B-cell associated markers and the activation of the gene for the heavy chain of the immunoglobulin M. The gene activation as determined by quantification of the mu mRNA with a fluorochrome labeled gene probe in situ in individual cells showed a wide spectrum of positivity which was correlated to increasing expression of B-maturation markers. There was also a correlation between the amount of cellular immunoglobulin as determined by immunofluorimetry. Quantitation of mRNA in individual cells may allow to determine the degree of gene activation in antigenically defined individual cells and may thus contribute a new tool for classification of normal and malignant cells.

Antigens, Differentiation↗
PubMed1987

Dose-response relationship in the treatment of idiopathic thrombocytopenic purpura with intravenous immunoglobulin.

The dose-response relationship in the intravenous immunoglobulin treatment of idiopathic thrombocytopenic purpura was studied in 20 adult patients in a multicenter prospective crossover trial. The rate of response increases from 3 out of 11 (27%) to 6 out of 10 treatment periods (60%) by raising the 7S-IgG dose given on 5 consecutive days from 164.50 +/- 24.55 to 359.65 +/- 58.62 mg/kg body weight. The onset and duration of response as well as the peak platelet count were found to be independent of the doses. A long-term benefit induced by intravenous immunoglobulin treatment could be achieved in 2 out of 14 patients with chronic idiopathic thrombocytopenic purpura.

Adolescent↗